Retina-Specific T Cells Provide Neuroprotection in A Model of Glaucoma

Abstract Glaucoma is a disease that leads to degeneration of retinal ganglion cells (RGC) and is potentially blinding if left untreated. Based on the concept of “beneficial autoimmunity”, we examined whether naïve, retina-specific T lymphocytes can provide neuroprotection to retinal ganglion cells in an optic nerve crush injury glaucoma model. Purified T cells from mice that express the transgenic R161H TCR for the retinal antigen IRBP, as well as eGFP (R161H-eGFP), were adoptively transferred into wild type (WT) mice. Also, irradiated bone marrow (BM) chimeras were stably engrafted with <10% circulating R161H-eGFP cells. Recipient mice were subjected to retrograde fluorogold labeling for quantification of RGC prior to an optic nerve crush injury. Retinas were imaged 4 or 7 days later for quantification of RGCs and donor R161H-eGFP T cells were detected by confocal microscopy. In both types of recipients, T cell influx into the eye and neuroprotection were apparent, but differed in kinetics. In adoptively transferred mice, R161H T cells were detected in the eye 4 days post injury and were associated with 27% less RGC loss compared to controls infused with normal polyclonal eGFP+ T cells (p<0.05). In the BM chimeric mice, major influx of R161H-eGFP cells occurred at 7 days post injury and was associated with a 16% statistically significant reduction in RGC loss. We conclude that naïve retina-specific T cells can mediate neuroprotection of retinal ganglion cells.